This invention relates to the method for the preparation of alkyl 4[2-(phthalimido)ethoxy]-acetoacetate. More particularly it relates to the preparation of ethyl-4-[2(phthalimido)ethoxy]-acetoacetate having formula (4) 
using 4-[2(phthalimido)-ethoxyacetic acid of formula (1). 
Ethyl-4-[2(phthalimido)ethoxy]-acetoacetate (4) is an important intermediate in the manufacture of anti-ischaemic and antihypertensive drug i.e. amlodipine having formula (5). 
In the prior art processes, ethyl 4-[2(phthalimido)-ethoxy] acetoacetate (4) has been hitherto obtained by O-alkylation of N-(2-hydroxyethyl) phthalimide with ethyl 4-chloroacetoacetate using sodium hydride as base (Simon F, Campbell, Peter E. Cross, John K. Stubs, U.S. Pat. No. 4, 572,909).
The draw backs of the known processes are 1) the use of sodium hydride as base which is known to be pyroforic and 2) the alkylating agent ethyl-4-chloroacetoacetate is known to have high toxicity (Oyo Yakuri, CA 107:110714, 1987).
The toxic symptoms consisted of the inhibition of CNS systems especially respiratory depression and the local irritation of tissues. The O-alkylation is carried out in anhydrous THF and reaction conditions are stringent (xe2x88x9210xc2x0 C.).
The main object of the present invention is to prepare of alkyl 4-[2(phthalimido)-ethoxy]-acetoacetate of formula (4) using easily available raw materials.
It is another object of the invention to provide a process for the preparation of alkyl 4-[2(phthalimido)-ethoxy]-acetoacetate of formula (4) using easily available raw materials such as phthalimide, solvent such as toluene and base such as potassium carbonate, Meldrum acid and thionyl chloride, which overcomes the drawbacks of the prior art methods enumerated above.
Accordingly the present invention provides an improved process for the preparation of alkyl-4-[2(phthalimido)-ethoxy]-acetoacetate having formula (4), 
which comprises reacting 2-(phthalimido)-ethoxyacetic acid of the formula (1) 
with thionyl chloride to obtain the compound having formula (2) 
followed by reacting compound of formula (2) with Meldrum""s acid having formula (3) 
in an organic solvent in the presence of a base at a temperature ranging between 5-10xc2x0 C., acidifying with dilute HCI, extracting in an organic solvent, removing the solvent and refluxing the residue with alcohol to obtain the desired product.
In one embodiment of the invention the 2[(2-phthalimido)ethoxy]acetic acid of formula (1) is reacted with thionyl chloride in the presence of an organic solvent.
In another embodiment of the invention, the solvent used for the reaction of 2[(2-phthalimido)ethoxy]acetic acid of formula (1) is selected from toluene, dimethyl formamide and a mixture thereof.
In another embodiment of the invention, the organic solvent used for the reaction of compound of formula (2) with Meldrums acid of formula (3) is selected from ethylenedichloride and methylenedichloride.
In another embodiment of the invention, the organic solvent used for the extraction of alkyl-4-[2(phthalimido)-ethoxy]-acetoacetate having formula (4) is selected from ethylenedichloride, methylenedichloride and toluene.
In another embodiment the base used for the reaction of compound of formula (2) with Meldrums acid of formula (3) is selected from triethylamine and pyridine.
The invention provides a method to prepare various alkyl-4-[2(phthalimido)-ethoxy]-acetoacetate (4) useful in the manufacture of anti-hypertensive and anti-ischaemic drugs. The present investigation consists of an improved and elegant process for the preparation of alkyl-4-[2(phthalimido)-ethoxy]acetoacetate (4).